Mechanisms for the regulatory effect of prostaglandin E2/ prostaglandin E receptor 4 on high mobility group box-Ⅰ protein in lipopolysaccharide-induced sepsis in mouse peritoneal macrophage
10.11817/j.issn.1672-7347.2017.08.004
- VernacularTitle:脂多糖诱导小鼠腹腔巨噬细胞炎性反应中前列腺素E2/前列腺素E受体4调控高迁移率族蛋白Ⅰ的机制
- Author:
Xiaoliang WANG
;
Yong ZHANG
;
Yanna SI
;
Yajie XU
;
Hongguang BAO
;
Xiaoming BAI
;
Jing LENG
- Keywords:
mouse peritoneal macrophages;
prostaglandin 2;
high mobility group box-1 protein;
PI3K/Akt signaling pathway
- From:
Journal of Central South University(Medical Sciences)
2017;42(8):889-898
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.Methods:Ihe mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages.The PGE2,prostaglandin E receptor (EP) 4 agonist,EP4 RNAi,and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage.The levels of HMGB 1 was determined by Western blot.Results:Compared with LPS alone treatment,the expression of HMGB 1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS,and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P<0.05);compared with the PGE2+LPS treatment,the level of HMGB1 was decreased after knockdown of EP4 receptor expression (P<0.05);compared with EP4 receptor agonist +LPS treatment,there was no difference in HMGB1 levels in mice after the treatment with DN.CREB plasmid to suppress CREB function (P>0.05);compared with LPS alone treatment,the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P<0.05),which were blocked by EGFR inhibitor.Once Akt specific inhibitor was used before EP4 and LPS treatment,the expression of HMGB1 was declined (P<0.05).Conclusion:PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor,which may be related to the activation of EGFR/PI3K/Akt signaling pathway.
